During his university years he studied with Werner Jaeger, Heinrich Rickert, Richard Kroner, Karl Hampe, Friedrich Baethgen, Eduard Norden, and Ulrich von Wilamowitz. He also attended lectures by noted philosophers such as Ernst Cassirer, Edmund Husserl, and Karl Jaspers. In 1928, he earned his doctorate from the University of Heidelberg under Ernst Hoffmann with a dissertation on Plotinus.[1] He did postdoctoral work at the universities of Berlin and Freiburg.[2] At Freiburg, Kristeller studied under the philosopher Martin Heidegger from 1931 to 1933.[3] The Nazi victory in 1933 forced Kristeller to move to Italy. At his arrival, Giovanni Gentile secured for him a position as lecturer in German at the Scuola Normale Superiore in Pisa. It was at the Scuola Normale that Kristeller completed his first great works in the Renaissance: the Supplementum Ficinianum (1937) and The Philosophy of Marsilio Ficino (1943). In 1939, he fled Italy, due to the enactment of Mussolini's August 1938 racial laws, to live in the USA. Thanks to the help of Yale University historian Roland Bainton, he sailed from Genoa in February 1939 and by March was teaching a graduate seminar at Yale on Plotinus. However Kristeller taught for only a short time at Yale University until moving to Columbia University, where he taught until his retirement in 1973, as Frederick J. E. Woodbridge Professor of Philosophy. He continued to be an active researcher after he retired. Paul Kristeller received the Serena Medal of the British Academy in 1958, the Premio Internazionale Galileo Galilei in 1968 and the Commendatore nell'Ordine al Merito della Repubblica Italiana in 1971.

An especially important achievement is his Iter Italicum (the title recalls Iter Alemannicum and other works of Martin Gerbert), a large work describing numerous uncatalogued manuscripts. After decades of neglect, Kristeller's lengthy, erudite essay of the early 1950s, "The Modern System of the Arts", in Journal of the History of Ideas, proved to be an influential, much reprinted classic reading in Philosophy of Art.

Kristeller was the chief inspirer of the Catalogus Translationum et Commentariorum, the ongoing project that aims to chart the fortune of all extant classical works through the Middle Ages and Renaissance, serving as Founder and Editor-in-Chief for the first two volumes and Associate Editor for the next five volumes.